WO1995000110A1

WO1995000110A1 - Composition for oral cavity

Info

Publication number: WO1995000110A1
Application number: PCT/JP1994/001019
Authority: WO
Inventors: Yasukuni Nishida; Midori Morishima; Maimi Ohta; Tetsuo Gomi; Yoshihiro Harada
Original assignee: Lion Corporation
Priority date: 1993-06-28
Filing date: 1994-06-24
Publication date: 1995-01-05
Also published as: US5711937A; AU6983594A; CN1126433A

Abstract

A composition for oral cavity which is excellent in antibody stability, can produce a satisfactory antibody effect even after being stored for long, and gives a comfortableness in its use. The composition comprises an antibody selected from those present in blood, egg and milk, and contains l-menthol and a perfume component selected from carvone, anethole, cineole, methyl salicylate, eugenol, ethyl butyrate and cinnamaldehyde in a ratio of 9:1 to 2:8 by weight.

Description

Specification

Oral composition Technical field

The present invention relates to an oral composition containing an antibody having a prophylactic or therapeutic effect on dental caries and periodontal disease, and more specifically, the effect of the above antibody is sufficiently exerted even after long-term storage. The present invention relates to an oral composition having a good feeling of use.

Background art

It has specifically acted on Streptococcus mutans bacteria as an active ingredient to prevent dental caries, preventing the adherence of these bacteria to tooth surfaces. Researches have been conducted to incorporate an antibody having an inhibitory effect on plaque formation into an oral composition such as dentifrice.

In addition, an antibody that specifically acts on periodontal disease-causing bacteria as an active ingredient for preventing periodontal disease and suppresses the colonization of the periodontal disease-causing bacteria in the oral cavity is used in toothpaste, etc. Studies have also been carried out to formulate it into oral compositions.

However, the above antibody has a problem of inactivation due to the effect of an anion activator contained in the composition for oral cavity and the like. Therefore, various techniques for stabilizing and blending the antibody have been studied.

On the other hand, since the oral composition is used in the oral cavity, it must have an excellent feeling in use. Therefore, it is necessary to mix various fragrance ingredients to improve the feeling of use according to the type of consumer's taste, etc. The problem was that it had an unfavorable effect on body stability.

For this reason, development of an oral composition excellent in antibody stability and usability is desired.

Disclosure of the invention

An object of the present invention is to provide an antibody-containing oral composition having excellent antibody stability, exhibiting the effects of the antibody satisfactorily even when stored for a long period of time, and having a good feeling in use.

As a result of intensive studies to achieve the above object, the present inventors have found that an oral composition containing an antibody selected from blood antibody, egg antibody and milk antibody contains carbon, , Cineole, methylsilyl citrate, eugenol, ethyl butylate and cinnamic aldehyde, and a menthol by weight ratio When used together at a ratio of 1: 9 to 8: 2, unexpectedly, the above antibody is stably maintained, and the antibody activity remains sufficiently after long-term storage, and the effect is sufficient. In addition, the present inventors have found that the composition for oral cavity can be obtained, and that the present invention can provide an excellent feeling in use.

Accordingly, the present invention relates to an oral composition containing an antibody selected from a blood antibody, an egg antibody and a milk antibody, comprising carbon, an anet, a cineole, and a methinoresali. Perfume ingredients selected from citrate, eugeno-nore, ethyl butyrate and cinnamaldehyde, and ^ -menthol in a weight ratio of 1: 9 to 8: Provide an oral composition characterized by being blended in a ratio of 2. The oral composition of the present invention can be used for dentifrices such as toothpaste, lubricating toothpaste, powdered toothpaste, liquid dentifrice, etc., liquid mouth fresheners such as mouse mouthwash, solid mouth such as troches and the like. It can be prepared as a cooling agent, chewing gum, etc., and contains antibodies selected from blood antibodies, egg antibodies, and milk antibodies as active ingredients, as well as carbon and alpha. Perfume ingredients selected from netul, cineol, methylsilyl citrate, eugeno monol, etilbutyrate and cinnamic guanole dehydro, and-weight of menthol They are used together in a ratio of 1: 9 to 8: 2.

Here, as the above antibody, antibodies against various antigens can be used. For example, antibodies against various antigens of cariogenic bacteria can be used. Antibodies such as Streptococcus mutans bacteria can be used as the cariogenic bacteria.

In addition, antibodies against various antigens of periodontal disease-causing bacteria can be used. The term periodontal disease-causing bacterium is generally characterized by a deep etiological causal relationship with periodontal disease. , Ponole Platinum * Genji-no-kurisu, Actino-myces * Pi-cos, Plebotera 'intermedia, fuzokuterimu' Ata, Capnosite, Faga spp., Oykenella's coordination, Campirono, Kuta-lectas, Nocteroides-des It can be used with spiros such as auto-physics, treponemal and dentic cola.

The above-mentioned antibody includes the above-mentioned cariogenic bacteria, the whole cells of the above-mentioned periodontal disease-causing bacteria, fimbria, capsule, bacterial cell extract or bacterial cell surface-derived polysaccharide. As an antigen, a blood antibody or a milk antibody obtained by immunizing a mammal with the antigen, or an egg antibody obtained by immunizing a poultry is used. be able to. Alternatively, a monoclonal antibody prepared according to a known method may be used.

As a method for preparing the antibody, that is, a method for immunizing an animal, a method for purifying an antibody, and the like, ordinary methods can be employed. Specific examples of the preparation are shown in Reference Examples below.

In the oral composition of the present invention, one kind of the above-mentioned antibodies may be used alone, or two or more kinds may be used in combination. The amount of the antibody is not particularly limited, but is usually 0.0001 to 10% (% by weight, hereinafter the same) in the oral composition, preferably 0.02. Up to 5% can be blended.

In the present invention, the above-mentioned composition for oral cavity containing antibody contains carbon, ether, cineole, methylsyl resylate, eugenol, ethyl butylate and cinnami One or two or more selected from alkaldehydes are blended, and among them, Anetole can be suitably used.

The above-mentioned perfume ingredients may be blended as a single substance, or may be blended with essential oils and the like containing them, such as spare mint oil in the case of carbon. .

Further, the menthol used in combination with the above-mentioned perfume component may be blended as a single substance. However, essential oils and the like containing such a menthol, such as peppermint oil and Japanese husk oil, are used. May be blended.

The mixing ratio of the above-mentioned perfume ingredient and menthol is based on the weight ratio. The ratio is 1: 9 to 8: 2, preferably 2: 8 to 7: 3.By blending within this ratio range, the antibody can be stably combined. It is possible to improve the feeling of use by adding a refreshing sensation, a richness, and an appropriate taste to the skin. On the other hand, if the blending ratio of the fragrance component is less than the above range, the taste will be insufficient due to lack of body and taste, and if the fragrance component is more than the above range, The objective of the present invention cannot be achieved because the stability of the antibody is reduced and the cooling feeling is insufficient.

It is desirable that the blending amount of the above-mentioned perfume component be 0.01 to 0.5% of the whole composition, and if it is less than 0.01%, the feeling of use may be reduced, and it may exceed 0.5%. In addition, the stability of the antibody may be reduced, and the usability may be reduced.

Further, in the present invention, it is desirable that the total blending amount of the above-mentioned perfume component and menthol be 0.1 to 5%, particularly 0.3 to 3% of the whole composition. If the total amount is less than 0.1%, the body may not be sufficiently rich and refreshing, and if it exceeds 5%, the taste may become too strong, and even if a larger amount is used. The stability of the antibody may not be further improved.

In the oral composition of the present invention, in addition to the above antibody as an active ingredient, dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme, and the like are included. Fungicides such as enzymes, chlorhexidines, triclosan, and cetinolepyridine chloride, alkali metal monofluorophosphine, Fluoride such as sodium fluoride, stannous fluoride, stannous compound, epsilon-aminocapronic acid, tranexamic acid, alanine G Indone, Aminoleminium Chloride Hydroxylantoin, Dihydrocholesterol, Daritinolenitrin, Azulene, Biminin E, sodium chloride, water-soluble inorganic phosphoric acid compounds, etc. may be added. In particular, when an alkaline metal monofluorophosphate such as sodium monofluorophosphate is used in combination with the above antibody, the antibody is more stabilized, and the antibody can be stored for a long period of time. It is desirable because the survival rate can be kept high. In this case, it is preferable that the addition amount of the alkali metal monofluorophosphoric acid be 10 ppm to 100 ppm as fluorine. Examples of the water-soluble inorganic phosphoric acid compound include orthophosphoric acid, pyrrolic acid, potassium salt of polyphosphoric acid, and sodium salt. The phosphoric acid rim salt of the above phosphoric acid is preferred.

In addition to the above-mentioned perfume ingredients, aliphatic alcohols having 7 to 17 carbon atoms and their esters, terpenic hydrocarbons, phenol ethers, aldehydes, keto Other perfume ingredients such as lactone and lactone, and essential oils may be blended as long as the effects of the present invention are not impaired.

The composition of the present invention may contain, as other components, commonly used components according to the type of the composition. For example, in the case of dentifrices, aluminum oxide, aluminum hydroxide, calcium phosphate dihydrate or anhydride, abrasive gel are used as abrasives. , Ginoleconosilicate, ginoleic anhydride, phenolic phenol, phenolic phosphate, phenolic acid, aluminum phosphate Um, insoluble sodium metaphosphate, magnesium tertiary phosphate, magnesium carbonate, calcium sulfate, synthetic tree One or more kinds of fats and the like can be blended usually in a blending amount of 20 to 90% of the whole, especially 20 to 6% in the case of toothpaste. In the present invention, it is preferable to use a silica-based compound as the main polishing agent, which can further reliably improve the stability of the antibody and the dentifrice itself. it can. Examples of the silica-based compound include sedimentable silica, silica gel, aluminosilicate, dinorenosilicate, and the like. It is preferable that the particle size is 1 to 30 m from the viewpoint of usability.

In addition, dentifrice compositions include potassium alginate, gum alginate, gum alginate, potassium alginate, sodium carboxyl cellulose, sodium alginate, and the like. Vinyl alcohol, veegum, etc. may be blended (the blending amount is usually 0.3 to 5%). Particularly when an alkali metal monofluorophosphate is blended as an effective component, the strength of the composition and the feeling of use may increase the strength of the composition. It is desirable to use salt together. In this case, the force lagenan is a normal force lagenan (Katsuno I).

Cutlet, compared to (Z-Zitter mixed system). It is especially preferable to use c-strength ragenan because c-strength ragenan (c-strength ragenan) is effective in preventing skin roughness of the dentifrice composition. .

Further, as thickeners, sonorebit, glycerin, propylene glycol, 1, 3-butylene glycol, polyethylene glycol, ki It can be used in the form of a mixture of silica, malt, lactit and the like (the amount is usually 10 to 70%). In this case, it is desirable to use propylene glycol as the thickener dispersion, Since the residual ratio of the antibody due to storage decreases when it is mixed in an appropriate amount, it is desirable to mix sorbitol as the main thickener and use propylene glycol in combination. .

In addition, it is also available in the following formats: Sodium Laura Nolesanorefette, Lauroil Zanoreco Cinete, Hiolerefore Innorefonate, Taurate, Rauri Noremonogure Anionic activators such as ceramide sulfate, laurinolemono glyceride, sulfonate, stone, etc., diethanolamine laurate, and stearyl monog Lyseraid, sucrose fatty acid ester, lactose fatty acid ester, lactotol fatty acid ester, multitol fatty acid ester, polyoxyethylene sonorebitanmo Nonionic activators such as nostelate, amphoteric activators such as betaine and amino acid

(Usually 0.5 to 7%), saccharin sodium, stepioside, neohesperidinoresin hydrodynamic compound, taumatine, glycyrrhizin, perica Sweeteners such as raltin, preservatives such as sodium parabenzoate and sodium benzoate, and components such as gelatin and peptone may be added.

In the case of producing toothpaste, it can be produced by kneading the above components with an appropriate amount of water. The toothpaste composition thus obtained was prepared by laminating aluminum tube and aluminum foil on both sides with plastic or the like. It can be used by being housed in a predetermined container such as a mineral tube, a plastic tube, a bottle-shaped container, or an aerosol container.

In addition, an oral composition other than toothpaste can be produced according to a conventional method using a commonly used base material. In the oral composition of the present invention, blood antibodies, egg antibodies, and milk antibodies are stably retained, their effects are effectively exhibited over a long period of time, and a wide selection of flavor components can be made. It has good usability.

Hereinafter, the present invention will be described specifically with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples.

In addition, all% in each case are weight%.

(Antibody preparation method A)

First, an antigen was prepared by the following method.

(l) Preparation of PAc antigen

The PAc antigen was prepared according to Lena et al.'S method (J. General Microbiology, 122, 217-225, 1981), and S. mutans 10449 was cultured in 20 liters of TPY dialysis medium and centrifuged. The supernatant was fractionated using 60% ammonium sulfate, and the precipitate was collected. The precipitate was dissolved in 10 mM Tris-HCl buffer (pH 7.5), dialyzed against the same buffer, adsorbed on DEAE-Sephacel column chromatography, and subjected to NaC ^ concentration gradient. Eluted better. Furthermore, the target fraction was concentrated, and then purified by gel filtration using Sepharose 6B.

(2) Preparation of whole cell antigen

S.mutans 10449 was cultured in 20 liters of TTY medium at 37 ° C under aerobic conditions for 18 hours. The culture was separated into bacterial cells and culture supernatant by centrifugation at 8000 rpm for 20 minutes. After harvesting, the cells were washed three times with a phosphate buffer (PBS), three times with sterile distilled water, and then lyophilized. (3) Preparation of bacterial cell-bound dalcosyltransferase (GTF)

S.mutans 10449 was cultured in 20 liters of TTY medium at 37 ° C under aerobic conditions for 18 hours. The ± 咅 nutrient solution was separated into bacterial cells and culture supernatant by centrifugation at 8000 rpm for 20 minutes. After harvesting, the cells were washed three times with physiological saline, and extracted with a solution containing 4 M urea and 0.5 M salt at room temperature for 1 hour with gentle stirring. The cells were separated from the cells by centrifugation (8000 rpm, 20 minutes) and dialyzed against a 10 mM phosphate buffer (pH 6.0). The resulting precipitate was removed by centrifugation, and the supernatant was subjected to a 60% saturated ammonium sulfate precipitation treatment, and the obtained precipitate was recovered under the above-mentioned centrifugation conditions. This precipitate was dissolved in the above buffer solution, dialyzed against the same buffer, the precipitate in the dialysate was removed by centrifugation, and the supernatant was sterilized by filtration through a 0.22 m filter sterilization membrane, and used for immunization. The antigen was used.

(4) Preparation of water-soluble glucan synthase (GTF-S)

S.mutans 10449 was cultured in 20 liters of TTY medium at 37 ° C under aerobic conditions for 18 hours. The culture was separated into bacterial cells and culture supernatant by centrifugation at 8000 rpm for 20 minutes. The culture supernatant was subjected to a 55% saturated ammonium sulfate precipitation treatment, and the resulting precipitate was collected by centrifugation. Next, the precipitate was dissolved in Histidine-HC buffer (pH 6.0) and dialyzed against the same solution. The resulting precipitate was removed by centrifugation, and the supernatant was sterilized by filtration through a 0.22 m filter sterilizing membrane. Then, a 2.5 x 25 cm cap of Porino Buffer PBE 94 (Pharmacia) was used. Ram. For the fraction adsorbed on the column, use Polybuffer 74 (manufactured by FANOREMACIA). It was eluted selectively by the pH gradient. Strong GTF activity was observed in the fraction at pH 5.5 to 4.9. The fractions were collected and subjected to 80% saturated ammonium sulfate precipitation to obtain a precipitate. The precipitate was dissolved in 10 mM phosphate buffer (pH 6.0) and dialyzed against the same solution. Further, the precipitate formed in the solution was removed by centrifugation, and the supernatant was used as an antigen.

The GTF activity was measured using a 10 cz sample as a substrate and a 0.2 M phosphate buffer (pH 6.0) containing 20 mM ["C-Gnorecose" sucrose (O.OSciZmol). After reacting at 37 ° C for 1 hour, the entire amount of the reaction solution was spotted on filter paper (1 X lcm), washed with methanol, and the remaining methanol on the filter paper was removed. GTF activity was calculated by measuring the amount of radioactivity incorporated in the glucan insoluble in glucose, and the activity of transferring 1 mol of glucose to glucan per minute was defined as 1 unit.

Next, a chicken egg antibody, an antiserum antibody, and a breast milk antibody against each of the antigens obtained above were prepared by the following methods.

(1) Preparation of chicken egg antibody

A 0.5 m solution containing lmgZm of the above antigen and 0.5 m £ of FIA (complete incomplete adjuvant) were mixed at a ratio of 1: 1 to obtain a W / 0 type emulsion. The obtained emulsion was injected into the left and right pectoral muscles of chickens 0.5 m each, and after the first immunization, immunization was continued every week and eggs were collected one month later. When the antibody titer decreased, immunization was repeated as appropriate, and egg collection was continued for about one year. Next, add an equal volume of water to the yolk separated from the egg, add an equal volume of a 0.5% suspension of larginan suspension, and stir. The supernatant was obtained by centrifugation at 8000 rpm for 20 minutes, and this was used as an antibody-containing fraction (WSF), and the antibody titer was measured and used. From the above procedure, a liquid 10 m_β of 80-320 units / m £ (lmg / m ί) of chicken egg antibody was obtained.

(2) Preparation of breast milk antibody

Prepare the antigen at a concentration of 50 βg / mi to 200 mgm m and mix it with an equal amount of incomplete Freund's adjuvant, and use this solution for pregnant goats, egrets, puppies and pomas. The immunization was performed by injecting 0.3 m / injection subcutaneously into the back of each individual, and the antigen was mixed with incomplete Freund's adjuvant every 2 to 4 weeks. After three immunizations, colostrum was collected after delivery. Next, an equal volume of 0.9% saline was added to the colostrum sample, and the mixture was centrifuged at 1200 rpm for 60 minutes.The upper layer of fat and sediment were removed, and an intermediate liquid component was collected. In addition, the pH was adjusted to 4. Further, the mixture was centrifuged at 5000 rpm for 30 minutes, and the supernatant was neutralized with tris-hydroxylaminomethan, and then ammonium sulfate was added to achieve 75% saturation. Was collected. The precipitate was dialyzed against a phosphate buffer to obtain an antibody component (inner solution) of breast milk. A solution of colostrum antibody 10-20 units Zm £ (lmg / m £) was obtained.

(3) Preparation of antiserum antibody

After immunization four times as described above, blood was collected and coagulated, and the centrifuged supernatant was used as a sample. To the antiserum was added ammonium sulfate to 50% saturation, and the resulting precipitate was dialyzed against a phosphate buffer to obtain an antiserum antibody (inner solution). Serum antibody approx. 80-320 units / mi (1 mg / mi) was obtained.

The antibody titer of each antibody was measured by the following method using the bacterial cell agglutination test. Measurement method of antibody titer:

(1) Cell suspension

One or two colonies of S. mutans 10449 on TYC agar medium were inoculated into a 200-m BHI liquid medium, cultured anaerobically at 37 ° C for 18 hours, and then collected, and 0.1% bovine serum albumin was collected. The plate was washed three times with the added physiological saline (BSA saline). The washed cells were suspended in BSA saline, 0 D _55. Adjusted to _nm 1.0. The cell suspension was prepared at the time of use.

(2) Sample antibody

Antibodies diluted at a dilution factor of 20, 30, 50, 70, and 90 were each diluted 2 ^n- fold.

(3) Operation method

After mixing and mixing 50 ^ diluted antibody and 50 ^ cell suspension on a microplate, the mixture was allowed to stand at 37 ° C for 3 hours and further at 4 ° C overnight.

(4) Determination of bacterial cell aggregation

After standing overnight, the bottom of the microplate was observed. If no microbial spots appeared, the agglutination was positive. If even a small number of spots were observed, the agglutination was negative.

[Examples 1 to 9, Comparative Examples 1 and 2]

A toothpaste composition having the formulation shown in Table 1 was prepared, and the amount of antibody immediately after preparation and after storage at 40 ° C for one month was measured by an ELISA method using an immunizing antigen to determine the residual ratio of the antibody. . The result is The post value was taken as 100% and used as the denominator, and the value after storage at 40 ° C was determined as the residual activity in terms of numerator. The feeling of use of these toothpaste compositions was evaluated by a sensory test using a specialized panel. Table 1 shows the results.

(table 1)

Antibody residual rate evaluation criteria Usability evaluation criteria

〇: Residual rate 70% or more 〇: Good

△: Residual rate 30% or more and less than 70% X: Flavor is monotonous and uncomfortable

X: Abundance less than 30% V: Insufficiency due to lack of cooling (Table 2)

Example Example Example Example Example Example Example Toothpaste composition Component 4 5 6 7 8 9 Water-free gay acid 20% 20% 20% 20% 20% 20% 30 30 30 30 30 30 ゝ

Note 9Π n Δ onυ Carboxymethyl cell l.U

Rosinium 1.80 1.0 i.U l.U

, / No

Tsu no ^ no no \ so] /

No / No 1.2 1.2 1.2 1.2 Sulfate 1.2 1.2

Purinoren Ethanoron 1.0 1.0 1.0 1.0 1.0 1.0 Amide

Gelatin 1.0 1.0 1.0 1.0 1.0 1.0 Carbon 0.4-1--One cinema-0.3-One-One methyl salicylate--0.5 One--Eugenol- ― ― 0.1 ― ― Ethyl butyrate ― ― one ― 0.1 ― Cinamic aldehyde ― ― ― ― ― 0.3

£ 1ment 0.5 0.5 0.5 0.5 0.5 0.5 Saccharin 0.1 0.1 0.1 0.1 0.1 0.1 Orange oil 0.05 0.05 0.05 0.05 0.05 0.05 Benzaldehyde 0.02 0.02 0.02 0.02 0.02 0.02 foot 0.5 0.5 0.5 0.5 0.5 0.5 PA c

Anti-horse serum antibody 0.2 0.2 0.2 0.2 0.2 0.2 Water residue

Total 100.00 100.00 100.00 100.00 100.00 100.00 Antibody persistence

(Stored at 40 ° C for 1 month) 〇〇〇〇〇 (Usability ((〇〇〇〇〇 (Antibody preparation method B)

First, an antigen was prepared by the following method.

(1) Preparation of Whole Cell Antigen of Borfu romonas gingivalis Ponolephyromonas ginginalis 381 (FERM BP-1027) was added with hemin and menadione. After culturing in heavy broth for 2 days, the cells were collected. This was washed with PBS (phosphate buffer; pH 7.4), treated with 0.5% formalin overnight, and washed three times with PBS to obtain whole cell antigen.

(2) Preparation of pilus antigen of Borfu ilomonas gingivalis Porphyromonas gingivalis cultivated for 2 days in the same manner as above was collected, washed, and then washed with glass beads in PBS for 2 days. The mixture was gently stirred and passed through an injection needle (No. 25) three times to separate the pili from the cells. Then, the pilus layer of the supernatant was separated by centrifugation at 8,000 rpm for 15 minutes, dialyzed, and freeze-dried to obtain pilus antigen.

(3) Preparation of capsular antigen of Borfu romonas gingivalis The cells collected in the same manner as above were suspended in PBS containing 0.01M EDTA, and reacted at 60 ° C for 30 minutes. After passing through the injection needle three times, the capsule was separated from the cells. Next, the supernatant from which the cells were removed by centrifugation at 8,000 rpm for 15 minutes was further subjected to ultracentrifugation at 40,000 rpm for 2 hours, and the sediment was used as a capsular antigen.

(4) Preparation of bacterial cell surface polysaccharide antigen of actinotinoles actinomycetem commutans

Actinobacillus actinomycetem commutance Y4 strain (ATCC 43718) was added to the tod with 1% yeast extract. Was inoculated into preparative broth between 37 ° C, 3 days in Lee Nkyubeta one containing 5% C0 _2. Cultured. After harvesting, the cells were washed three times with physiological saline, suspended in saline, and subjected to auto-creep treatment at 121 ° C for 15 minutes. 'After cooling, the mixture was centrifuged at 10,000 X g for 20 minutes to separate the supernatant, physiological saline was added again to the precipitate, and the above-described extraction operation was repeated. The resulting supernatant was collected, dialyzed sufficiently against distilled water, and lyophilized. This was used as the cell surface polysaccharide antigen.

Next, a chicken egg antibody, an antiserum antibody, and a breast milk antibody against each of the antigens obtained above were prepared.

(1) Preparation of chicken egg antibody

A 0.5 m solution containing lmgZmi containing the above antigen and 0.5 m of FIA (incomplete adjuvant in Freund) were mixed at a ratio of 1: 1 to obtain a W / 0 type emulsion. The obtained emulsion was injected into the left and right pectoral muscles of chickens 0.5 m each, and after the first immunization, immunization was continued every week and eggs were collected one month later. When the antibody titer decreased, immunization was repeated as appropriate, and egg collection was continued for about one year. Next, add an equal volume of water to the yolk separated from the egg, add an equal volume of a suspension of 0.5% λ-force raginan, stir, and centrifuge at 8000 rpm for 20 minutes to obtain a supernatant. , Which was defined as the chicken egg antibody standard σ.

(2) Preparation of antiserum antibody

Prepare the antigen at a concentration of nom to 200 mgZm and mix it with an equal volume of incomplete Freund's adjuvant, which is used for goats, egrets, sea lions, horses and sheep. Immunize by subcutaneously injecting into the back subcutaneously at a rate of 0.3 m £ / animal, and every 2-4 weeks After immunization three times with a mixture of the antigen and incomplete Freund's adjuvant, blood was collected and allowed to coagulate, and the centrifuged supernatant was collected to obtain an antiserum sample. A precipitate obtained by adding ammonium sulfate to this antiserum to 50% saturation was dialyzed with a phosphate buffer to obtain an antiserum antibody sample.

(3) Preparation of breast milk antibody

Pregnant goats, magpies and sheep were immunized four times in the same manner as above, and colostrum was collected after delivery. Next, an equal volume of 0.9% saline was added to the colostrum sample, and the mixture was centrifuged at 1200 rpm for 60 minutes.The upper layer of fat and sediment were removed, and an intermediate liquid component was collected. In addition, it was adjusted to PH4.0. The mixture was further centrifuged at 5000 rpm for 30 minutes, and the supernatant was neutralized with Tris-N-doxymethylethylaminomethane, and then ammonium sulfate was added to achieve 75% saturation. The deposited precipitate was collected. The precipitate was dialyzed against phosphate buffer, and the resulting milk milk antibody was used as α-mouth.

[Example 10-: L8, Comparative Examples 3 and 4]

The toothpaste compositions having the formulations shown in Tables 3 and 4 were prepared, and the amount of antibodies immediately after preparation and after storage at 40 ° C for one month was measured by the ELISA method using the immunizing antigen. I asked. The results were obtained by setting the value immediately after preparation to 100% as the denominator, and the value after storage at 40 ° C as the numerator residual rate. The feeling of use of these toothpaste compositions was evaluated by a sensory test using a specialized panel. Tables 3 and 4 show the results. In the following examples, the amounts (%) indicate weight%. In addition, Ag is the best Mi g, P g is Ponorro romance Ginzino << Lis, AV is. マ、 P P P P, P i is Ple Media, Fn is a nucleus / nucleatum, Cr is a camphoronecta / rectus, and Bf is a nocteroides · Focusing, Td indicates Treponema's denticola.

(Table 3)

Antibody residual rate evaluation criteria Usability evaluation criteria

〇: Residual rate 70% or more 〇: Good

X: Residual rate less than 30% V: Insufficient feeling of use due to insufficient cooling (Table 4)

(Example 19) Dentifrice

Calcium phosphate dibasic dihydrate 50.0%

\? 1. レ、、、、、 L

P10.0

■> ノ

So 7 100.0 ^ +,

No j 1.0 no / * i 'no no ^, no sonore; 7 "noreno e 1.0

4, L

ノ Γ ― 一ノ j

レ 0.38 to ⁰ no / ヽ — 1 ί; ゝレ,〉

Note / field rb 0.6. Eugenol 0.03 Anethole 0.17 Saccharin 0.1 Ethanol 2.0 Dextranase 0. 02 Anti-PAc goat milk antibody or anti-Pg bacterial cell 0.2 Surface polysaccharide sheep serum antibody

water.

100. 0%

(Example 20) Dentifrice

Ganhydride 30.0% Glycerin 30.0 Sonorebit 20.0 Canoleboxet Noreosenoloose 1.0 Sodium rubber Sozoresonoref Gate 1 • 2-Menthol 0 • 1 Force knob 0.05 Spare mint oil 0.4%. 1 Mint oil 0.3 Saccharin 0.1 Ethanol 2.0 sodium fluoride 0.1 Anti-PAc horse serum antibody or anti-Pg whole bacterial cell 0.1 Horse serum antibody

Zi

100.0%

(Example 21) Dentifrice

Aluminum hydroxide 45.0% sonore bit 20.0 force lagenan 0.5 cane box resornolose lose 1.0 Sucrose monolaurate 2.0-mentol 0.6 peppermint oil 0.2 cineole 0.4 saccharin 0.1 anti-PAc milk antibody 0.3

^

00.0%

(Example 22) Dentifrice

Aluminum hydroxide 45.0% Sonorebit 20.0 Force Lagenan 0.5 Canolebox Remelose Noloose 1.0 Laurenoregienosolamide 1.0 Sucrose Monolaureate 2.0 Mentol 0.6 ぺ, ミ Mint oil 0.2 Cinéo isole 0.4 Saccharin 0.1 Anti-Pg fimbrial serum antibody 0.2 Anti-A a Fibrin horse serum antibody 0.2

Ζί

100.0%

(Example 23) Dentifrice

Phosphoric acid canolesum 25.0% Carboxymethylcellulose 1.0 Power lagenan 0.5 Sonorebit 35.0 Propylene glycol 3.0

Ν—Rauroinolemethyl Taurine Lithium Trium 0.5 Gelatin 1.0 Paraxoxybenzoic Acid Ethyl 0.2 Sacchar Linnatrium 0.1 £ No.0.6 Methyl salicylate 0.3 Monophosphoric acid sodium phosphate 0.7 Anti-PAc chicken egg antibody or anti-AV fimbrial egg antibody 0.4 Water _ 1_

100.0%

(Example 24) Dentifrice

Aluminum hydroxide 40.0% Canole box Nose senorum mouth mouth sodium 1.0 power lagenan 0.5 sonore bit 35.0 propylene glycol 3.0

N — Myristonitrinomethylaluminum Trinitrate 0.5 ぺ Peptide 1.0 Paraoxymethyl benzoate 0.2 Saccharinnatrium 0.1 Control 0.5 0.5. 1 mint oil 0.2 cinnamon aldehyde 0.15 snow, ° ismix Freno 1 0.05 anti-PAc sheep serum antibody or anti-Pi bacterial cell 0.5 surface polysaccharide sheep serum antibody

Top

00.0%

(Example 25) Dentifrice

Gay acid anhydride 20.0% Canoleoxymethyl cellulose cellulose 1.0 Sonore bit 50.0 Polyethylene glycol 5.0

N-palmitoinolemethyl taurine sodium 0.5 casein 1.0 sodium sodium benzoate 0.2 saccharin sodium 0.1

^ — Menthol 0.3 0.3 Cineorse 0.1 Ethyl petitate 0.01 Futidani sodium 0.2 Anti-GTF chicken egg antibody 0.3 L Remaining

100.0%

(Example 26) Dentifrice

Maleic anhydride 20.0% strength sodium hydroxide cellulose sodium 1.0 sodium hydroxide 50.0 polyethylene glycol 5.0 N — panore mitoinoleme Chiltaurin sodium 0.5 Casein 1.0 Paraxium sodium benzoate 0.2 Saccharin sodium trium 0.1-Ment nore 0.3 Cine Mono 0.1 0.1 Petite 0.01 Tranexamic acid 0.1 Anti-Fn whole cell chicken egg antibody 0.3 2l

100.0%

(Example 27) Mouthwash

Ethanol nodule 20.0% One-toned nodle 0.2 mm. 1 Mint oil 0.2 Eugenol 0.1 Cineol 0.05 Anetol 0.03 Saccharin 0.05 Rauryl Jetano NoreMad 0.3 To the mouth Anti-GTF horse serum antibody or anti-Cr bacterial body 0.1 Surface polysaccharide goat serum antibody

Ζί;

100.0%

(Example 28) Mouthwash

Sonorebit 10.0% Ethanol Nore 20.0 ミ — Millistone Inoline Methanourine Natrium 0.5 Sucrose Stearate Ester 1.0 ぺTide 0.5 Paraoxymethyl benzoate 0.1 Stepioside 0.1, mentor 0.2 0.2 methyl salicylate 0.3 cinnamo sorbet 0.1 technobutyl citrate 0.05 dextran 0.2 0.2 sodium fluoride 0.2 anti-Aa surface polysaccharide chicken egg antibody 0.2 Z

100.0%

(Example 29) Mouthwash

Sonorebit 10.0% Ethanol 20.0 Ν— Myristinolemethyltaurin sodium 0.5 sucrose sugar stearate ester 1.0 ぺPeptide 0.5 Methyl parabenzoyl benzoate 0.1 Stepioside 0.1-Ment-in-one 0.2 Methyl-sali-cylate 0.3 Sinamic vanaaldehyde 0.1 Ethanol butylate 0.05 Dextranase 0.2 Cetylpyridinium chloride 0.05 Anti-Bf whole cell chicken egg antibody 0.2 100.0%

(Example 30) Mouthwash

Solbit 10.0% Ethanol 20.0 N—Stearoin Ethanol

POE (20) Sorbitan monolate 1.0 Collagen 0.5 Methyl parabenzoyl benzoate 0.1 Saccharin sodium 0.1 0.1 M 0.05 force bonbon 0.1 spear mint oil 0.3mm. Mint oil 0.3 Anti-PAc milk antibody or anti-Td cells 0.4 Surface polysaccharide milk antibody

Z:

00.0%

[Example 31] Tablet

Arabic gum 6.0% Bud sugar 72.0 Gelatin 3.0 mentor 0.2 cine 0.1 0.1 Benzaldehyde 0.05 Sodium Alcohol Renoate 0.1 Anti-PA c sheep; milk antibody or anti-Aa capsular sheep milk antibody 0.1

100.0%

[Example 32] Game

Gambase 43.9% Calcium carbonate 2.0 Water 15.0 Sugar 29.0 Sucrose palmitate 1.0 Phanolose 4.0 Phanolose 3.0 Menthol 0.6 Power Norebon 0.4 Phenomix Mix Freon 1.0 Anti-PAc chicken egg antibody or anti-Pg fimbrial egg antibody 0.1

Ζί

00.0%

Claims

The scope of the claims

1. An oral composition containing an antibody selected from blood antibodies, egg antibodies and milk antibodies contains carbon, phenol, cineole, methinoresylate, and eugeno. It is characterized by blending a fragrance component selected from one ole, etinole butyrate and cinnamon aldehyde with one menthol in a weight ratio of 1: 9 to 8: 2. Oral composition.

2. The oral composition according to claim 1, wherein the antibody is an antibody against cariogenic bacteria.

3. The oral composition according to claim 2, wherein the cariogenic bacterium is Streptococcus mitogen.

4. The oral composition according to claim 1, wherein the antibody is an antibody against periodontal disease-causing bacteria.

5. Periodontal disease-causing bacteria are Actinobacillus, Actinomycetin commutans, Pozzoleiromonas genzino << Lith, Actinomyces viscos, Prevote La Intermedia, Fuzonoctelium * Nuclea tam, Capnosite Faga spp., Eukenella collodenum, Ki Jumpers, such as rectifiers, speakers, and treponema denticola. 5. The oral composition according to claim 4, which is a rotater.